A history of hookworm vaccine development

Schneider, Brigitte; Jariwala, Amar; Periago, María Victoria; Gazzinelli, Maria Flávia; Bose, Swaroop; Hotez, Peter J.; Diemert, David; Bethony, Jeffrey M.

doi:10.4161/hv.7.11.18443

Cited by 40 publications

(23 citation statements)

References 83 publications

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“…Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms 4,5 . Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease 6,7 .…”

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confidence: 99%

The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families

Schwarz

Antoshechkin

et al. 2015

Nat Genet

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Hookworms infect over 400 million people, stunting and impoverishing them1–3. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms4,5. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease6,7. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs)8. Genes downregulated during early infection included ion channels and G protein–coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.

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confidence: 99%

The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families

Schwarz

Antoshechkin

et al. 2015

Nat Genet

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“…A great deal of progress has been made on development of vaccines against human infections with hookworms, beginning with animal studies and currently involving clinical trials [43]. Efforts to develop vaccines against human infection with S. stercoralis have been limited, although there have been excellent results in an animal model using a single recombinant diagnostic antigen as the vaccine against S. stercoralis [44].…”

Section: Control Of S Stercoralismentioning

confidence: 99%

A Public Health Response against Strongyloides stercoralis: Time to Look at Soil-Transmitted Helminthiasis in Full

et al. 2013

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Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. Specific stool techniques for the detection of larvae of S. stercoralis, like Baermann's and Koga's agar plate, despite superiority over direct techniques are still suboptimal. New serologies using recombinant antigens and molecular-based techniques offer new hopes in those areas. The use of ivermectin rather than benzimidazoles for its treatment and the need to have curative regimens rather than lowering the parasite burden are also unique for S. stercoralis in comparison to the other STH due to its life cycle, which allows reproduction and amplification of the worm burden within the human host. The potential impact on STH of the benzimidazoles/ivermectin combinations, already used for control/elimination of lymphatic filariasis, should be further evaluated in public health settings. While waiting for more effective single-dose drug regimens and new sensitive diagnostics, the evidence and the tools already available warrant the planning of a common platform for STH and S. stercoralis control.

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“…The generation of antigen-specific IgE antibodies secondary to vaccination or pre-existing in the population would likely impair the protective efficacy of immunization with that specific candidate vaccine [ 37 ]. In response to a systemic vaccination these circulating parasite-specific IgE antibodies can lead to a deleterious allergic response, as seen with the hookworm Na -ASP-2 vaccine [ 38 ]. Serum-specific IgE to total IgE ratio is a clinical indicator of allergen-specific response [ 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm

et al. 2018

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Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD). Current control measures focused on mass deworming have had limited success due to low drug efficacies. Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission. Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model. The recombinant WAP protein (rTm-WAP49), as well as a single, highly conserved repeat within WAP (fragment 8) expressed as an Na-GST-1 fusion protein (rTm-WAP-F8+Na-GST-1), generate a strong T helper type 2 (Th2) immune response when delivered as subcutaneous vaccines formulated with Montanide ISA 720. Oral challenge with T. muris infective eggs following vaccination led to a significant reduction in worm burden of 48% by rTm-WAP49 and 33% by rTm-WAP-F8+Na-GST-1. The cellular immune correlates of protection included significant antigen-specific production of Th2 cytokines IL-4, IL-9, and IL-13 by cells isolated from the vaccine-draining inguinal lymph nodes, parasite-draining mesenteric lymph nodes, and spleen in mice vaccinated with either rTm-WAP49 or rTm-WAP-F8+Na-GST-1. The humoral immune correlates included a high antigen-specific ratio of IgG1 to IgG2a, without eliciting an IgE-mediated allergic response. Immunofluorescent staining of adult T. muris with WAP antisera identified the worm’s pathogenic stichosome organ as the site of secretion of native Tm-WAP protein into the colonic mucosa. Given the high sequence conservation for the WAP proteins from T. muris and T. trichiura, the results presented here support the WAP protein to be further evaluated as a potential human whipworm vaccine candidate.

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A history of hookworm vaccine development

Cited by 40 publications

References 83 publications

The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families

The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families

A Public Health Response against Strongyloides stercoralis: Time to Look at Soil-Transmitted Helminthiasis in Full

Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm

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